PROJECT SUMMARY Effective radiation therapy for lung and abdominal cancer is currently limited by tumor motion. The traditional method of compensating for tumor motion is to expand the target volume by a large margin surrounding the tumor, such that the total volume irradiated often is much larger than the tumor itself. Reducing the size of the motion-related margin is therefore the key to improving the efficacy of radiotherapy for tumors that move with the breathing of the patient, notably tumors of the lung. A new technique is needed to solve this problem. The new technique, in addition to reducing the margin substantially, must fulfill certain requirements: it must be easy to adapt the technique to existing radiotherapy facilities; no major or costly additional equipment should be needed; no additional treatment time should be required; and the patient's comfort should not be compromised. To achieve these goals, we have invented an adaptive real-time dynamic tumor-tracking strategy that we call Dose-Rate-Regulated Tracking (DRRT). The beam-delivery sequence is preprogrammed prior to treatment, based on four-dimensional images of the tumor and the associated breathing pattern. The deviations between the sequence determined in this imaging session and the tumor position at the time of beam delivery can be compensated by adaptively adjusting the treatment dose rate. This in turn alters the temporal structure of the preprogrammed treatment sequence. We hypothesize that the proposed scheme for real-time tumor tracking will reduce the motion-related margin required for proper dose coverage of lung tumors to less than 2 mm. The overall objective of this project is to develop the DRRT technology and to test its clinical feasibility and accuracy. We believe that our proposed study will result in a clinically feasible, accurate, and practical radiotherapy technique that will eliminate the current margin limitation caused by respiration-induced tumor motion. The resulting smaller margin and reduced collateral damage to normal lung and other organ structures will allow many more patients to receive the benefits of radiation therapy. Among these benefits are greatly increased flexibility in treatment planning, far less damage to critical structures, and the ability to make use of hypofractionation treatments that have recently been shown to greatly improve local control and survival. The result should be a substantial increase in the life expectancy and quality of life of many, perhaps most, lung-cancer patients.